The starting point for defining effective treatment protocols is a clear understanding of the etiology and pathogenesis of a condition. In periodontal diseases, this understanding has been hindered by a number of factors, such as the difficulty in differentiating primary pathogens from nonpathogens in complex biofilm structures. The introduction of DNA sequencing technologies, including taxonomic and functional analyses, has allowed the oral microbiome to be investigated in much greater breadth and depth. This article aims to compile the results of studies, using next‐generation sequencing techniques to evaluate the periodontal microbiome, in an attempt to determine how far the knowledge provided by these studies has brought us in terms of influencing the way we treat periodontitis. The taxonomic data provided, to date, by published association and elimination studies using next‐generation sequencing confirm previous knowledge on the role of classic periodontal pathogens in the pathobiology of disease and include new species/genera. Conversely, species and genera already considered as host‐compatible and others less explored were associated with periodontal health as their levels were elevated in healthy individuals and increased after therapy. Functional and transcriptomic analyses also demonstrated that periodontal biofilms are taxonomically diverse, functionally congruent, and highly cooperative. Very few interventional studies to date have examined the effects of treatment on the periodontal microbiome, and such studies are heterogeneous in terms of design, sample size, sampling method, treatment provided, and duration of follow‐up. Hence, it is still difficult to draw meaningful conclusions from them. Thus, although OMICS knowledge has not yet changed the way we treat patients in daily practice, the information provided by these studies opens new avenues for future research in this field. As new pathogens and beneficial species become identified, future randomized clinical trials could monitor these species/genera more comprehensively. In addition, the metatranscriptomic data, although still embryonic, suggest that the interplay between the host and the oral microbiome may be our best opportunity to implement personalized periodontal treatments. Therapeutic schemes targeting particular bacterial protein products in subjects with specific genetic profiles, for example, may be the futuristic view of enhanced periodontal therapy.